We propose to study the relations between prospectively collected data on occupation, occupational exposures, medical history, and medication use and risk of amyotrophic lateral sclerosis (ALS) in a case-control study nested within the entire population of Denmark between the years 1985 and 2009 using the Danish Registry systems. We will also examine whether any of the potential risk factors-in particular, statin or hormone replacement therapy (HRT) use-affect survival with ALS. The population of Denmark is approximately 5 million men and women and the Danish Registry system allows for the linkage of data for each individual on, among other things, occupational history, hospital use, and prescription medication. These data go back as far as 1964 for occupational history. There are roughly 100-150 new ALS cases each year in Denmark, thus the proposed investigation will include an estimated 2838 incident ALS cases between 1985 and 2009 and 100 controls for each case, making it the largest study of ALS to date within a very large, well-defined and completely enumerated population, with prospectively collected exposure data with respect to disease onset and a long follow-up time. PUBLIC HEALTH RELEVANCE: This study will examine whether particular environmental factors increase the risk of developing amyotrophic lateral sclerosis (ALS). In, particular, we will focus on lead and formaldehyde exposure, trauma, and use of statin and hormone replacement therapy medications. Furthermore, we will assess whether these factors affect the survival of patients with ALS.